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C. MECHANISM OF CONTRACTION
1. Slow waves give rise to spike potentials, which stimulate cell contraction.
2. The initial phase of contraction is triggered by an increase in cytoplasmic calcium, released from the
sarcoplasmic reticulum, as occurs in skeletal muscle.
3. Sustained contraction is mediated by continued influx of Ca 2+ into the cytoplasm from the interstitium,
through voltage-gated calcium channels on the cell membrane.
4. Calcium combines with the protein calmodulin to form the calcium-calmodulin (Ca 2+ -CaM) complex and
activates myosin light-chain kinase (MLCK).
5. MLCK in turn phosphorylates the myosin cross-bridges, exposing binding sites for actin.
6. Actin and myosin then form cross-bridges that contract the muscle cell.
7. Relaxation occurs when Ca2+ has been pumped back into the sarcoplasmic reticulum so that the Ca 2+ -
CaM complex can no longer be formed.
D. REGULATION OF CONTRACTION
1. Most smooth muscle has intrinsic pacemaker activity, but smooth muscle activity can be modulated by the
autonomic nervous system (i.e., it is generally not under voluntary control).
2. Sympathetic and parasympathetic nerves are distributed to all organ systems in the body and stimulate
smooth muscle activity in many organs at once.
3. For example, in the fight-or-flight response, sympathetic stimulation causes a myriad of responses such as
pupillary dilation, dilation of coronary arteries, decreased intestinal motility, and bronchial dilation.
4. In general, parasympathetic stimulation has the opposite effects.
Clinical note: In Chagas disease, infection with the protozoan parasite Trypanosoma cruzi (found in South
America) can cause destruction of the myenteric plexus of the enteric nervous system, resulting in severely
impaired regulation of intestinal smooth muscle contraction, particularly in the esophagus.
Clinical manifestations may include difficulty swallowing (dysphagia), chest pain from esophageal distention,
and frequent bouts of pneumonia caused by aspiration of esophageal contents. The myenteric plexus of the
colon may also be destroyed, causing toxic megacolon.
VI. CARDIAC MUSCLE
A. STRUCTURE
1. Similar to smooth muscle, the cells are interconnected through gap junctions and function as a syncytium
(Table 1-9).
2. Similar to skeletal muscle, they contain sarcomeres and are striated in appearance.

B. Mechanism of contraction
1. Similar to skeletal muscle, contraction occurs through a sliding filament mechanism.
2. In contrast to skeletal muscle, extracellular Ca2+ plays a substantial role in triggering contraction.
3. Similar to smooth muscle, contraction occurs in an “all or none” manner.

Pharmacology note: The fact that extracellular calcium plays such an important role in stimulating cardiac
muscle contraction is exploited by calcium channel blocking drugs such as diltiazem and verapamil. Calcium
channel blockers reduce heart rate and contractility without adversely affecting skeletal muscle functioning
and are therefore useful for treating hypertension and a myriad of cardiac conditions.

C. REGULATION OF CONTRACTION
1. Similar to smooth muscle, cardiac cells have an unstable RMP that allows them to generate their own
electrical pacemaker activity.
2. Rate of contraction (chronotropy), strength of contraction (inotropy), rate of conduction (dromotropy), and
rate of relaxation (lusitropy) are further regulated by the autonomic nervous system.
3. Sympathetic stimulation has positive chronotropic, inotropic, dromotropic, and lusitropic effects through the
binding of norepinephrine and epinephrine to adrenergic receptors.
4. Parasympathetic stimulation has negative chronotropic, inotropic, dromotropic, and lusitropic effects
through the binding of ACh to muscarinic receptors.
TABLE 1-9. Comparison of Skeletal, Cardiac, and Smooth Muscle
FEATURE SKELETAL MUSCLE CARDIAC MUSCLE SMOOTH MUSCLE
Location Bone to bone Heart Around hollow organs
(gastrointestinal tract,
airways, ureters)
Cell morphology Large-diameter, Uninuclear and/or Small diameter
multinucleated cells binucleated, branched
cells
Striated Yes Yes No
Gap junctions No Yes Yes
Sarcomeres Yes Yes No, actin inserts into
dense bodies instead of
Z disks
Innervation Somatic nervous Autonomic nervous Autonomic nervous
system system system
Type of contraction Graded All or none All or none
Mechanism of Sliding filament Sliding filament Calcium-calmodulin–
contraction mechanism mechanism induced activation of
myosin light-chain kinase
Origin of calcium Sarcoplasmic reticulum Sarcoplasmic reticulum Sarcoplasmic reticulum
and extracellular fluid and extracellular fluid
Troponin Yes Yes No
Postsynaptic Nicotinic receptor at Adrenergic and muscarinic Muscarinic receptors
receptor neuromuscular junction receptors throughout the widely distributed along
heart the cell surface
Action potential Short duration Long duration Long duration
Resting membrane Stable Unstable Rhythmic fluctuations
potential (slow waves), which give
rise to spike potentials
Conduction of Restricted to that Functional syncytium, Functional syncytium,
action potentials particular muscle fiber, conducted through gap conducted through gap
action potential travels junctions junctions
bidirectionally along
fiber
Pacemaker activity No Yes Yes
Effect of denervation Atrophy Will function adequately Still able to maintain tone
(e.g., heart transplant), but
ability to exercise will be
dependent on circulating
catecholamines only
Examples of Muscular dystrophy, Congestive heart failure
CREST syndrome,
pathology myositis achalasia, Chagas
disease
CREST, Calcinosis cutis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia.

Clinical note: The most common-onset muscular dystrophy, Duchenne muscular dystrophy, is an X-linked
trait and is caused by a defect in the gene for dystrophin, a protein necessary for sarcolemma stability in
striated muscle. Breakdown of sarcolemma results in calcium influx, enzyme activation, and muscle necrosis;
fatty tissue and connective tissue fill the spaces once occupied by muscle, giving muscle a
pseudohypertrophic appearance. Muscle weakness starts in the legs, with wide-based gait, hyperlordosis,
and what appears to be hypertrophy of muscle. Patients are usually wheelchair-bound by 12 years of age.
Lack of dystrophin in the brain leads to mental retardation. The mortality rate is 100%, and death is caused
not by skeletal muscle defects but mostly by the absence of dystrophin in cardiac muscle, which results in
fibrosis of the myocardium and subsequent heart failure, pulmonary congestion and arrhythmias.